Mechanisms related to increased susceptibility of the elderly lung to ventilator-induced lung injury: A scoping review.

Rapid population aging has markedly increased the exposure of elder humans to invasive mechanical ventilation (MV). Mounting evidence suggests that aging fundamentally alters pulmonary structure and stress responses, predisposing the aged lung to ventilator-induced lung injury (VILI). However, the biological basis of this heightened vulnerability remains insufficiently synthesized. The review was conducted in accordance with the PRISMA 2020 guidelines. To this end, PubMed, Web of Science, and Scopus databases were consulted. From the 901 identified records, 22 studies met inclusion criteria after screening and full-text evaluation, encompassing in vitro experiments, animal models, and clinical investigations addressing age-ventilation interactions. Experimental studies consistently demonstrate an exaggerated inflammatory phenotype in aged lungs, characterized by increased IL-6 and TNF-α, intensified neutrophilic infiltration, and marked disruption of the alveolar-capillary barrier even under lung-protective strategies. Mechanistically, aging is associated with dysregulated renin-angiotensin signaling, endoplasmic reticulum stress activation, altered sphingolipid homeostasis, and upregulation of injury mediators including ADAM9 and MLCK2. In vivo models reveal worsened oxygenation, enhanced pulmonary edema, and increased mortality in aged subjects. Clinical studies corroborate an association between advanced age and adverse ventilatory outcomes, modulated by comorbidity burden and illness severity. Aging reshapes the biological response to ventilatory stress at structural, inflammatory, and molecular levels, establishing a distinct vulnerability phenotype. These findings underscore the need for age-informed ventilatory strategies and targeted translational research in geriatric critical care.